A Lung Adenocarcinoma Patient With a Rare EGFR E709_T710delinsD Mutation Showed a Good Response to Afatinib Treatment: A Case Report and Literature Review

Yu, Wei; Cui, Yueli; Guo, Yufeng; Li, Lei; Zeng, Liang

doi:10.3389/fonc.2021.700345

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…Previous case reports of EGFR PACC insertion deletion mutations in NSCLC indicate sensitivity to afatinib and other EGFR TKIs (gefitinib, erlotinib) ( 36 – 38 ), including a 23-month PFS response with afatinib ( 37 ). Case 4 achieved a PR with afatinib after PD on erlotinib, which is also consistent with a previous case study where clinical benefit with afatinib following prior erlotinib treatment was reported ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report

Christopoulos,

Herster,

Hoffknecht

et al. 2024

Front. Oncol.

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent first-line standard of care in unresectable EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). However, 10–20% of patients with EGFRm+ NSCLC have uncommon EGFR variants, defined as mutations other than L858R substitutions or exon 19 deletions. NSCLC harboring uncommon EGFR mutations may demonstrate lower sensitivity to targeted agents than NSCLC with L858R or exon 19 deletion mutations. Prospective clinical trial data in patients with NSCLC uncommon EGFR mutations are lacking. Afatinib is a second-generation TKI and the only Food and Drug Administration-approved drug for some of the more prevalent uncommon EGFR mutations. We present a series of seven case reports describing clinical outcomes in afatinib-treated patients with NSCLC harboring a diverse range of extremely rare mutations with or without co-mutations affecting other genes. EGFR alterations included compound mutations, P-loop αC-helix compressing mutations, and novel substitution mutations. We also present a case with NSCLC harboring a novel EGFR::CCDC6 gene fusion. Overall, the patients responded well to afatinib, including radiologic partial responses in six patients during treatment. Responses were durable for three patients. The cases presented are in line with a growing body of clinical and preclinical evidence that indicating that NSCLC with various uncommon EGFR mutations, with or without co-mutations, may be sensitive to afatinib.

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Section: Discussionmentioning

confidence: 99%

Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report

Christopoulos,

Herster,

Hoffknecht

et al. 2024

Front. Oncol.

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“…Additionally, Wei et al. ( 12 ) reported successful treatment of EGFR Exon 18 Insertion p.Glu709_Thr710delinsAsp mutated NSCLC with Afatinib, followed by Almonertinib after tumor progression. The progression-free survival for Afatinib was 23 months, which was nearly twice as long as in our reported case.…”

Section: Discussionmentioning

confidence: 99%

“…This study suggested that a combination of first generation TKIs and chemotherapy could be equally effective as treatment with Afatinib as a second generation TKI alone. Additionally, Wei et al (12) reported successful treatment of EGFR Exon 18 Insertion p.Glu709_Thr710delinsAsp mutated NSCLC with Afatinib, followed by Almonertinib after tumor progression. The progression-free survival for Afatinib was 23 months, which was nearly twice as long as in our reported case.…”

Section: Discussionmentioning

confidence: 99%

“…As the patient furthermore suffered from severe nausea and vomiting from cisplatin, we decided to end chemotherapy and initiate TKI-therapy with Osimertinib. This decision was based on case reports previously describing the use of TKIs for this particular EGFR mutation with variable success (9)(10)(11)(12). We began treatment with Osimertinib at the beginning of December 2021, starting with 80 mg taken orally once daily.…”

Section: Case Presentationmentioning

confidence: 99%

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Case Report: Durable therapy response to Osimertinib in rare EGFR Exon 18 mutated NSCLC

Cekay,

Arndt,

Dumitrascu

et al. 2023

Front. Oncol.

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Up to 20% of all non-small cell lung cancer patients harbor tumor specific driver mutations that are effectively treated with tyrosine kinase inhibitors. However, for the rare EGFR deletion-insertion mutation of exon 18, there is very little evidence regarding the effectiveness of tyrosine kinase inhibitors. A particular challenge for clinicians in applying tyrosine kinase inhibitors is not only diagnosing a mutation but also interpreting rare mutations with unclear therapeutic significance. Thus, we present the case of a 65-year-old Caucasian male lung adenocarcinoma patient with an EGFR Exon 18 p.Glu709_Thr710delinsAsp mutation of uncertain therapeutic relevance. This patient initially received two cycles of standard platinum-based chemotherapy without any therapeutic response. After administration of Osimertinib as second line therapy, the patient showed a lasting partial remission for 12 months. Therapy related toxicities were limited to mild thrombocytopenia, which ceased after dose reduction of Osimertinib. To our knowledge, this is the first report of effective treatment of this particular mutation with Osimertinib. Hence, we would like to discuss Osimertinib as a viable treatment option in EGFR Exon 18 p.Glu709_Thr710delinsAsp mutated lung adenocarcinoma.

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“…Another patient with inoperable stage IIB lung cancer and the same E709_T710delinsD mutation achieved up to 23 months of PFS with first-line afatinib treatment. After experiencing disease progression, the patient received almonertinib and demonstrated stable disease [ 22 ]. This finding suggests that afatinib followed by sequential almonertinib treatment may serve as a viable therapy for NSCLC patients with the EGFR E709_T710delinsD mutation.…”

Section: Afatinib’s Effectiveness In Curing Various Uncommon Egfr Mut...mentioning

confidence: 99%

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review

et al. 2023

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Afatinib, the world’s first irreversible ErbB family (containing four different cancer cell epidermal growth factor receptors, including EGFR, HER2, ErbB3, and ErbB4) inhibitor, is a second-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It can be used as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR-sensitive mutation or for patients with locally advanced or metastatic squamous lung cancer whose disease progresses during or after platinum-containing chemotherapy. Currently, with the use of third-generation EGFR-TKIs, afatinib is no longer clinically indicated as the first choice for patients with NSCLC who have EGFR-sensitive mutations. However, afatinib showed a considerable inhibitory effect in NSCLC patients with uncommon EGFR mutations (G719X, S768I, and L861Q) according to a combined post hoc analysis of the LUX-Lung2/3/6 trials. With the development of genetic testing technology, the detection rate of uncommon EGFR mutations is increasing. The aim of this paper is to describe in detail the sensitivity of rare EGFR mutations to afatinib and to provide information and a reference for those suffering from advanced NSCLC who have uncommon EGFR mutations.

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A Lung Adenocarcinoma Patient With a Rare EGFR E709_T710delinsD Mutation Showed a Good Response to Afatinib Treatment: A Case Report and Literature Review

Cited by 8 publications

References 19 publications

Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report

Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report

Case Report: Durable therapy response to Osimertinib in rare EGFR Exon 18 mutated NSCLC

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review

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